Genetically Engineered Virus Nanofibers as an Efficient Vaccine for Preventing Fungal Infection.
Genetically Engineered Virus Nanofibers as an Efficient Vaccine for Preventing Fungal Infection.
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基因工程病毒纳米纤维作为预防真菌感染的有效疫苗
DOI：
10.1002/adhm.201500930
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发表时间：
2016-04-06
影响因子：
10
通讯作者：
Mao C
中科院分区：
文献类型：
--
作者：
Huai Y;Dong S;Zhu Y;Li X;Cao B;Gao X;Yang M;Wang L;Mao C
白色念珠菌（Candida albicans，CA）是一种可引起免疫功能低下患者高发病率和死亡率的真菌。然而，在这些患者中预防CA感染仍然是一个艰巨的挑战。在此，从用分泌型乙酰基蛋白酶2（Sap 2）免疫可以预防感染的事实得到启发，提出使用丝状噬菌体，一种人类安全的病毒，其特异性地感染细菌（约900 nm长和7 nm宽），以展示Sap 2的表位肽在其侧壁上具有一个胞外多糖（EPS，具有Val-Lys-Tyr-Thr-Ser的序列），并因此用作预防CA感染的疫苗。然后将工程化的病毒纳米纤维和重组Sap 2（rSap 2）分别用于免疫小鼠。评价免疫小鼠的体液和细胞免疫应答。令人惊讶的是，病毒纳米纤维显著诱导小鼠产生与rSap 2一样强的免疫应答，并产生可以结合Sap 2和CA的抗体，以抑制CA感染。因此，在小鼠中用病毒纳米纤维免疫显著增加了CA感染小鼠的存活率。所有这些结果，沿着病毒纳米纤维可以通过感染细菌成本有效地大规模生产的事实，表明展示EPS的病毒纳米纤维可以成为抗真菌感染的候选疫苗。
Candida albicans (CA) is a kind of fungus that can cause high morbidity and mortality in immunocompromised patients. However, preventing CA infection in these patients is still a daunting challenge. Herein, inspired from the fact that immunization with secreted aspartyl proteinases 2 (Sap2) can prevent the infection, it is proposed to use filamentous phage, a human‐safe virus nanofiber specifically infecting bacteria (≈900 nm long and 7 nm wide), to display an epitope peptide of Sap2 (EPS, with a sequence of Val–Lys–Tyr–Thr–Ser) on its side wall and thus serve as a vaccine for preventing CA infection. The engineered virus nanofibers and recombinant Sap2 (rSap2) are then separately used to immunize mice. The humoral and cellular immune responses in the immunized mice are evaluated. Surprisingly, the virus nanofibers significantly induce mice to produce strong immune response as rSap2 and generate antibodies that can bind Sap2 and CA to inhibit the CA infection. Consequently, immunization with the virus nanofibers in mice dramatically increases the survival rate of CA‐infected mice. All these results, along with the fact that the virus nanofibers can be mass‐produced by infecting bacteria cost‐effectively, suggest that virus nanofibers displaying EPS can be a vaccine candidate against fungal infection.